U.S. patent number 5,376,361 [Application Number 08/003,603] was granted by the patent office on 1994-12-27 for method and compositions for topical application to the skin for prevention and/or treatment of radiation-induced skin damage.
Invention is credited to Nicholas V. Perricone.
United States Patent |
5,376,361 |
Perricone |
December 27, 1994 |
Method and compositions for topical application to the skin for
prevention and/or treatment of radiation-induced skin damage
Abstract
A method for the prevention and/or treatment of
radiation-induced skin damage, particularly ultraviolet-induced
skin burn (e.g., sunburn), in which a tocotrienol, a derivative
thereof or a vitamin E preparation enriched with tocotrienol or a
tocotrienol derivative, is topically applied to the exposed or
affected skin areas. A fat-soluble fatty acid ester of ascorbic
acid such as palmityl ascorbate is preferably applied with the
tocotrienol in association with a dermatologically acceptable
carrier. Tocotrienol augments the efficacy of sunscreens containing
compounds that reduce penetration of or absorb ultraviolet
radiation.
Inventors: |
Perricone; Nicholas V.
(Guilford, CT) |
Family
ID: |
21706656 |
Appl.
No.: |
08/003,603 |
Filed: |
January 13, 1993 |
Current U.S.
Class: |
424/59; 424/60;
514/474 |
Current CPC
Class: |
A61K
8/498 (20130101); A61K 8/676 (20130101); A61K
8/678 (20130101); A61K 31/35 (20130101); A61K
31/355 (20130101); A61K 31/60 (20130101); A61Q
17/04 (20130101); A61K 31/355 (20130101); A61K
31/60 (20130101); A61K 2300/00 (20130101); A61K
2300/00 (20130101) |
Current International
Class: |
A61K
31/60 (20060101); A61K 8/49 (20060101); A61K
8/67 (20060101); A61K 8/30 (20060101); A61K
31/355 (20060101); A61K 31/352 (20060101); A61K
31/35 (20060101); A61Q 17/04 (20060101); A61K
007/42 (); A61K 007/44 (); A61K 031/34 () |
Field of
Search: |
;424/59,60 ;514/474 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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291960 |
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Nov 1988 |
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EP |
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337464 |
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Oct 1989 |
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EP |
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2000507 |
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Jul 1970 |
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DE |
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52-61239 |
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May 1977 |
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JP |
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1152613 |
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Jul 1986 |
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JP |
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ZA75/6475 |
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May 1976 |
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ZA |
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Other References
Encyclopedia of Chem. Technology, 3rd ed. vol. 20, pp. 762-763,
1982. .
Grant & Hackh's Chemical Dictionary, 5th ed., pp. 529-530,
1987..
|
Primary Examiner: Ore; Dale R.
Attorney, Agent or Firm: St. Onge Steward Johnston &
Reens
Claims
We claim:
1. A method for preventing radiation-induced skin damage, said
method comprising topically applying to skin areas subject to such
damage an effective amount of an active ingredient selected from
the group consisting of tocotrienols and vitamin E preparations
enriched with tocotrienols.
2. A method according to claim 1 wherein the active ingredient is a
tocotrienol selected from the group consisting of
alpha-tocotrienol, beta-tocotrienol, gamma-tocotrienol, and
delta-tocotrienol.
3. A method according to claim 1 wherein said effective amount is
applied as a composition further comprising a reductant.
4. A method according to claim 3 wherein said reductant is a
fat-soluble fatty acid ester of ascorbic acid.
5. A method according to claim 4 wherein said fat-soluble fatty
acid ester of ascorbic acid is selected from the group consisting
of ascorbyl palmitate, ascorbyl laurate, ascorbyl myristate,
ascorbyl stearate, and mixtures thereof.
6. A method according to claim 5 wherein said fat-soluble fatty
acid ester of ascorbic acid is ascorbyl palmitate.
7. A method according to claim 1 wherein said active compound is
applied in the form of a sunscreen composition further comprising a
dermatologically acceptable carrier.
8. A method according to claim 7 wherein the sunscreen composition
contains a compound that reduces penetration of or absorbs
ultraviolet radiation.
9. A method according to claim 8 wherein the compound that reduces
penetration of or absorbs ultraviolet radiation is selected from
the group consisting of para-aminobenzoic acid, para-aminobenzoic
acid esters, cinnamates, benzophenone, anthranilate, titanium
dioxide, zinc oxide, iron oxide, and mixtures thereof.
10. A method according to claim 7 wherein the combination of the
compound and the carrier is in a form selected from the group
consisting of solutions, dispersions, creams, lotions, gels and
solid sticks.
11. A method according to claim 7 wherein the combination comprises
about 0.5% to about 5% by weight tocotrienol.
12. A method for the treatment of radiation-induced skin damage,
said treatment comprising topically applying to the affected skin
areas an effective amount of a composition comprised of a
dermatologically acceptable carrier and a tocotrienol composition
selected from the group consisting of
tocotrienols,
and a vitamin E preparation enriched with tocotrienols.
13. A method according to claim 12 wherein the composition further
comprises a fat-soluble fatty acid ester of ascorbic acid selected
from the group consisting of ascorbyl palmitate, ascorbyl laurate,
ascorbyl myristate, ascorbyl stearate, and mixtures thereof.
14. A method according to claim 12 wherein the tocotrienol is
selected from the group consisting of alpha-tocotrienol,
beta-tocotrienol, gamma-tocotrienol, and delta-tocotrienol.
15. A method according to claim 14 wherein the tocotrienol is
alpha-tocotrienol.
16. In a sunscreen composition comprising a compound that reduces
penetration of or absorbs ultraviolet radiation and a
dermatologically acceptable carrier, an improvement wherein, to
augment the efficacy of the sunscreen, said composition further
comprises a tocotrienol composition selected from the group
consisting of tocotrienols and vitamin E preparations enriched with
tocotrienols.
17. An improvement according to claim 16 wherein said tocotrienol
is selected from the group consisting of alpha-tocotrienol,
beta-tocotrienol, gamma-tocotrienol, and delta-tocotrienol.
18. An improvement according to claim 16 wherein the compound that
reduces penetration of or absorbs ultraviolet radiation is selected
from .the group consisting of para-aminobenzoic acid,
para-aminobenzoic acid esters, cinnamates, benzophenone,
anthranilate, titanium dioxide, zinc oxide, iron oxide, and
mixtures thereof.
19. An improvement according to claim 16 wherein the composition
further comprises a fat-soluble fatty acid ester of ascorbic acid
selected from the group consisting of ascorbyl palmitate, ascorbyl
laurate, ascorbyl myristate, ascorbyl stearate, and mixtures
thereof.
20. An improvement according to claim 19 wherein said tocotrienol
is D-alpha-tocotrienol.
Description
DESCRIPTION
1. Technical Field
The present invention relates to the topical application to the
skin of active agents, and/or preparations containing them, for the
prevention and/or treatment of radiation damage to the skin, and
particularly for the treatment of skin to protect it from
deleterious effects caused by excessive exposure to ultraviolet
radiation, as in the case of sunburn.
2. Background Art
Ultraviolet-induced burning of the skin is most commonly seen in
persons who have been excessively exposed to natural sunlight
(i.e., sunburn), but also can be seen in persons who have been
excessively exposed to ultraviolet radiation from non-sunlight
(artificial) sources, as may occur in tanning booths or incident to
application of ultraviolet radiation as part of a therapeutic
treatment. Cutaneous burn and other forms of skin damage also can
arise from excessive or prolonged exposure to other forms of
radiation outside the ultraviolet spectrum.
The clinical manifestations of ultraviolet-induced burn seen in
acute reactions is attributed to ultraviolet radiation in the range
of 290-320 nanometers, generally designated ultraviolet B (UVB)
radiation, although prolonged exposure to longer wavelength
ultraviolet A light (.about.320-400 nanometers) can produce mild
burn and marked hyperpigmentation.
The sunburn reaction is a complex inflammatory process causing
dyskeratotic cells, spongiosis, vacuolation of kertinocytes and
edema from capillary leakage, 12 to 24 hours after exposure to
light. In addition to redness and pain, blisters may evolve.
Chronic effects of UV light include degenerative changes of the
skin which can lead to premalignant and malignant growths of the
skin and degeneration of the dermal collagen.
The detrimental effects of sunburn have been postulated to be
related to a transfer of energy from ultraviolet radiation to the
skin, resulting in generation of excited oxygen species, such as
singlet oxygen, the superoxide anion, and hydroxyl radicals that
can damage lipid-rich membranes with the subsequent activation of
the chemical mediators of inflammation. It is well known that
ultraviolet B radiation releases arachidonic acid, which is quickly
oxidized to a variety of biologically active metabolites, such as
prostaglandins PGD2, PGE2, PGEF2. When arachadonic acid is oxidized
via the cyclo-oxygenase pathway, prostaglandins create marked
erythema. Arachadonic acid oxidized via the 5-lipo-oxygenase
pathway produces leukotrienes, which also can cause erythema and
edema. The free radicals created by ultraviolet radiation can also
damage the DNA of the cells, resulting in permanent injury,
premature aging, and carcinogenesis.
The clinical symptoms of ultraviolet burn are on a spectrum from
mild increased sensitivity of the skin to severe pain. It should
also be noted that damage to skin can be caused by other forms of
radiation, that is, ionizing radiation as well as longer wave
length radiation such as infrared, which can result in erythema and
pigmentation as well as premature aging and malignancy. These other
forms of radiation create damage by the same mechanism, i.e.,
generation of free radicals with subsequent damage to the cell
membrane and DNA.
Suggestions for dealing with sunburn and other forms of ultraviolet
radiation burn have predominantly been aimed at prevention through
use of topical compositions containing agents for absorbing
radiation, e.g., as exemplified by commercial sunscreen products.
More recently, attention has been directed to agents which address
the underlying processes involved in radiation-induced skin damage,
such as the earlier-noted free radical generation processes. In
this regard, investigations have been made with respect to the
antioxidants vitamin E and vitamin C to quench free radicals on the
surface of the skin and to protect lipid membranes intracellularly
(Wilson, R., Drug and Cosmetic Industry, 32-34, 38, and 68, August
1992).
Vitamin E is a fat-soluble vitamin necessary in the diet of many
species for normal reproduction, normal development of muscles,
normal resistance of erythrocytes to hemolysis, and various other
biochemical functions. The most widely accepted function of vitamin
E is an an antioxidant, protecting polyunsaturated fatty acids in
membranes and other cellular structures from attack by free
radicals. Vitamin E occurs in cereals (especially wheat germ and
corn), sunflower seed, rapeseed, soybean oil, alfalfa, lettuce, egg
yolk, and beef liver, and consists primarily of three molecular
species of tocol derivatives, the alpha-, beta- and
gamma-tocopherols, of which alpha-tocopherol is most important
because it has the widest distribution and greatest biological
activity.
Other tocopherols have been found in nature, including gamma-,
eta-, zeta.sub.2, zeta.sub.1 - and epsilon-tocopherol. The last two
species, which occur in cereal grains, have unsaturated hydrocarbon
tails and have been recently called tocotrienols (denoted alpha-
and beta-tocotrienol, respectively) because each has three double
bonds in the side chain, and this nomenclature distinguishes them
from tocopherols bearing saturated tails. Gamma-tocopherol is
claimed to be the most potent antioxidant of any tocopherol species
(The Merck Index, 11th ed., 1989, entries 9417 to 9423 and 9931),
but activity appears to be dependent on the system used for
measurement. Thus, in the in vitro systems of Burton, G. W., et
al., J. Am. Chem. Soc. 107:7073-7065 (1985), for example,
alpha-tocopherol was the most powerful antioxidant.
The antioxidant function of vitamin E per se is localized in the
chromanol nucleus, where the phenolic hydroxy group donates a
hydrogen atom to quench lipid radicals ibid., and Serbinova, E., et
al., Free Radical Biology & Med., 10:263-275 (1991)). The
antioxidant potency of vitamin E is determined by the efficiency of
the tocopherol in scavenging radicals and by the reactivity of the
chromanoxyl radical formed in further propagation of lipid
peroxidation or in the regeneration of the tocopherol due to
interaction of the chromanoxyl radical with reductants; the latter
does not propagate lipid peroxidation.
In homogenous solutions, the rate constants of the reaction between
the chromanol nucleus and radicals do not depend upon the length or
unsaturation of the tocopherol hydrocarbon tails, but mainly depend
on the number of methyl groups in the benzene ring of the chromanol
nucleus (Burton, G. W., et al., cited above). Similarly, the
reactivity of the chromanoxyl radical is mainly determined by
hindering effects of the methyl groups.
The situation is more complex in heterogenous membrane systems,
however, where vitamin E appears to owe its antioxidant potency not
solely to the chemistry of the tocopherol molecule but also to its
mobility and accessibility within the membrane (Serbinova, cited
above). In some systems, tocotrienols appear to have higher
antioxidant activity (ibid.). However, in others, direct
comparisons of antioxidant efficiency of tocopherols having
saturated tails with tocotrienols did not demonstrate decisive
differences in the activities of these two forms of vitamin E
(ibid. and Nakano, M., et al., Biochim. Biophys. Acta 619:274-286
(1980)).
DISCLOSURE OF THE INVENTION
The primary object of this invention is to provide methods and
compositions for prevention and/or treatment of radiation skin
burn, particularly ultraviolet skin burn, and most particularly
sunburn.
It is a more particular object of the invention to provide a
preventive regimen and/or therapy based upon topical application to
exposed or affected skin areas of an active agent or precursor
thereof, preferably in association with a dermatologically
acceptable carrier or vehicle such as a sunscreen.
These and other objects are accomplished by the present invention,
which provides a method and composition for the prevention and/or
treatment of radiation-induced skin damage, which comprises topical
application to the exposed or affected skin sites of an effective
amount of one or more tocotrienols or derivatives thereof or
vitamin E compositions enriched with tocotrienols or tocotrienol
derivatives. Reductants such as alpha-hydroxy acids, ascorbic acid
and the like, particularly fat-soluble fatty acid esters of
ascorbic acid, can, optionally, be utilized along with the
tocotrienol as a means for yet further enhancing the efficacy of
the therapeutic or prophylactic treatment.
In the preferred practice of the invention, the tocotrienol (or
derivative) or tocotrienol-enriched vitamin E is applied in
admixture with a dermatologically acceptable carrier or vehicle
(e.g., as a lotion, cream, ointment, soap, or the like) so as to
facilitate topical application and, in some cases, provide
additional therapeutic effects as might be brought about, e.g., by
moisturizing of the affected skin areas. As noted, reductants,
particularly ascorbyl fatty acid esters, e.g., ascorbyl palmitate,
can be advantageously included in the compositions. In some
embodiments, the dermatologically acceptable carrier is a sunscreen
composition.
The amount of tocotrienol or derivative thereof (hereinafter
referred to collectively as tocotrienol for ease of reference)
necessary to bring about enhanced prevention and/or therapeutic
treatment of radiation-induced skin damage is not fixed per se, and
necessarily is dependent upon the identity and form of tocotrienol
employed, the concentration of tocotrienol when employed as a
tocotrienol-enriched vitamin E preparation and/or with a carrier,
the amount and type of any additional reductant such as ascorbyl
fatty acid ester, when employed with the tocotrienol, the user's
skin type, and, where present, the severity and extent of the
patient's pathological skin condition. Generally, the tocotrienol
or composition containing it is topically applied in effective
amounts to skin areas which have been damaged or aged, or which are
susceptible to damage, by reason of radiation, especially
ultraviolet radiation.
BEST MODES FOR CARRYING OUT THE INVENTION
This invention is based upon the surprising finding that
tocotrienols or tocotrienol-enriched vitamin E compositions,
especially tocotrienols or tocotrienol-enriched vitamin E in
combination with a reductant, such as ascorbyl fatty acid ester,
augment the efficacy of sunscreens, including sunscreens that
contain ordinary vitamin E.
As used herein, the term "tocopherol" encompasses vitamin E
derivatives bearing saturated hydrocarbon tails having the
following general formula: ##STR1## and includes both natural
alpha-, beta-, gamma-, and delta-tocopherol as well as synthetic
derivatives and mixtures thereof. The term "tocotrienol"
encompasses their counter-parts bearing unsaturated tails,
including, but not limited to, four tocotrienols occurring in
sunflower seeds and vegetable oils and in African violets, which
have three double bonds in the side chain at the 3', 7' and 11'
positions in the formula set out above, denoted alpha-, beta-,
gamma- and delta-tocotrienol, their synthetic counterparts, and
mixtures thereof. The double bonds may be cis or trans or mixtures
thereof.
Tocotrienol or tocotrienol derivatives or mixtures thereof are
employed in this invention either in the substantial absence of
tocopherols wherein the compositions contain essentially no
tocopherol or in tocotrienol-enriched vitamin E preparations. By
"tocotrienol-enriched vitamin E preparations" is meant vitamin E
preparations containing a greater concentration of tocotrienol than
that found in preparations isolated from natural sources. These
tocotrienol-enriched vitamin E preparations can, for example, be
naturally-occurring vitamin E preparations to which tocotrienol has
been added or naturally occurring vitamin E preparations from which
a portion of tocopherol has been removed.
Preferred vitamin E preparations are isolated from natural sources,
but synthetic preparations may also be employed as well as mixtures
of natural and synthetic vitamin E. Tocotrienol-enriched vitamin E
preparations may be obtained by fractionating vitamin E
preparations to remove a portion of tocopherols and recover a
preparation more highly concentrated in tocotrienol. Preferred
tocotrienols are natural products isolated, for example, from wheat
germ oil, bran, or palm oil using high performance liquid
chromatography. D-alpha-tocotrienol is especially preferred in one
embodiment.
As with other vitamin E preparations, tocotrienol or
tocotrienol-enriched preparations include those containing
tocotrienol and, in some cases, tocopherol derivatives. These
typically include derivatives related to the phenolic hydroxyl
functionality, i.e., wherein it is reacted with an acid to form an
ester such as an acetate. However, the derivatives may also include
those involving other reactive groups known to those skilled in the
art. Where tocotrienol derivatives are employed, they must be
functionally equivalent to tocotrienol. Preferred derivatives
contain both the chromanol nucleus and three double bonds in the
hydrocarbon tail.
Vitamin E derivatives generally vary in consistency from viscous
oils to oily liquids. Therefore, tocotrienols or
tocotrienol-enriched vitamin E preparations can be applied neat to
skin areas subject to damage or damaged by radiation. However, only
effective amounts of tocotrienols are needed to prevent or treat
radiation-induced skin damage, so generally topical application to
exposed or affected skin sites is accomplished in association with
a carrier, and particularly one in which the active ingredient is
soluble per se or is effectively solubilized (e.g., as an emulsion
or microemulsion). It is necessary that the carrier be inert in the
sense of not bringing about a deactivation of the tocotrienol or
derivative, and in the sense of not bringing about any adverse
effect on the skin areas to which it is applied.
Suitable carriers include water, alcohols, oils and the like,
chosen for their ability to dissolve or disperse the active
ingredient at concentrations of active ingredient most suitable for
use in the preventive or therapeutic treatment. Generally, even low
concentrations of active ingredient in a carrier will be suitable,
requiring only that more frequent topical application be resorted
to. As a practical matter, however, to avoid the need for repeated
application, it is desirable that the topically applied composition
(i.e., tocotrienol or derivative or tocotrienol-enriched vitamin E
preparation plus carrier) be formulated to contain at least about
0.5% by weight, and in some embodiments at least about 3% by
weight, and in other embodiments at least about 3 to 10% by weight,
of the active ingredient, and accordingly, carriers will be chosen
which can solubilize or disperse the active ingredient at such
concentrations.
While the carrier for the tocotrienol or derivative or
tocotrienol-enriched vitamin E preparation can consist of a
relatively simple solvent or dispersant such as water or oils, it
is generally preferred that the carrier comprise a composition more
conducive to topical application, and particularly one which will
form a film or layer on the skin to which it is applied so as to
localize the application and provide some resistance to washing off
by immersion in water or by perspiration and/or aid in the
percutaneous delivery of the active agent. Many such compositions
are known in the art, and can take the form of lotions, creams,
gels or even solid compositions (e.g., stick-form preparations).
Typical compositions include lotions containing water and/or
alcohols and emollients such as hydrocarbon oils and waxes,
silicone oils, vegetable, animal or marine fats or oils, glyceride
derivatives, fatty acids or fatty acid esters or alcohols or
alcohol ethers, lecithin, lanolin and derivatives, polyhydric
alcohols or esters, wax esters, sterols, phospholipids and the
like, and generally also emulsifiers (nonionic, cationic or
anionic), although some of the emollients inherently possess
emulsifying properties. These same general ingredients can be
formulated into a cream rather than a lotion, or into gels, or into
solid sticks by utilization of different proportions of the
ingredients and/or by inclusion of thickening agents such as gums
or other forms of hydrophillic colloids. Such compositions are
referred to herein as dermatologically acceptable carriers.
Many preferred embodiments of this invention contain a reductant in
addition to tocotrienol. Some embodiments, for example, employ
alpha-hydroxy acids such as glycolic acid, hydroxymethylglycolic
acid, lactic acid, glucuronic acid, galacturonic acid, gluconic
acid, glucoheptonic acid, alpha-hydroxybutyric acid,
alpha-hydroxyisobutyric acid, alpha-hydroxyvaleric acid,
alpha-hydroxyisovaleric acid, alpha-hydroxycaproic acid,
alpha-isocaproic acid, tartronic acid, tartaric acid, malic acid,
hydroxyglutaric acid, hydroxyadipic acid, hydroxypimelic acid,
muric acid, citric acid, isocitric acid, saccharic acid,
dihydroxymaleic acid, dihydroxytartaric acid, and dihydroxyfumaric
acid or derivatives of hydroxy acids such as pyruvic acid, methyl
pyrivate, ethyl pyruvate, isopropyl pyruvate, benzoylformic acid,
methyl benzoylformate, and ethyl benzoylformate.
Other embodiments employ ascorbic acid as a reductant, most
preferably fat-soluble fatty acid esters of ascorbic acid (vitamin
C) in addition to tocotrienol. The more oxidation-resistant
saturated fatty acid esters of ascorbic acid are preferred,
including, but not limited to, ascorbyl laurate, ascorbyl
myristate, ascorbyl palmitate, ascorbyl stearate, and ascorbyl
behenate. As denoted herein, where fatty acid esters are described,
e.g., ascorbyl stearate, compositions having predominantly that
ester, e.g., predominantly stearate, are included. The esters may
be prepared using hydrogenated oils or fats, or fractions thereof,
and contain small amounts of another ester. Ascorbyl stearate
prepared using canola, for example, commonly contain about 4%
ascorbyl palmitate.
The combination of tocotrienol or tocotrienol-enriched vitamin E
preparations and a fat-soluble vitamin C fatty acid ester in a
dermatologically acceptable carrier is especially advantageous in
sunscreen compositions because tocotrienol augments the efficacy of
sunscreens. By "sun-screen" is meant any topical preparation
containing a substance that absorbs or reduces penetration of
ultraviolet radiation partially, such as, for example compositions
containing para-aminobenzoic acid and/or its esters, cinnamates,
benzophenone, anthranilate, and the like, or totally, such as, for
example, compositions containing titanium dioxide, zinc oxide, iron
oxide, and the like. Preferred sunscreens formulated with
tocotrienol according to this invention have a sun protective
factor (SPF) of at least 3, most preferably from at least about 6
to about 23.
The effectiveness of tocotrienols and tocotrienol derivatives,
especially when employed in combination with a reductant such as
ascorbyl fatty acid esters, can be postulated as resulting from the
antioxidant properties of tocotrienol per se, which properties are
unexpectedly retained and provided to a high degree when used in
concert with ascorbyl fatty acid esters when these are delivered in
combination to the skin in an extremely effective manner in an oil
phase. The mechanism of the effect is not well understood, but may
be related to the anti-oxidant properties of the active compounds
and/or their interference with chemical reactions.
In terms of a possible explanation for the effectiveness of
tocotrienol in the prevention or treatment of radiation damage to
the skin, it is noted that tocotrienol, as an antioxidant, can
scavenge free radicals such as the oxygen radicals created by
exposure of cells to radiation, as well as the generation of free
radicals produced by normal metabolism extracellularly and
intracellularly. Ascorbic acid is a powerful reducing agent that
can prevent oxidative damage and regenerate chromanoxyl radicals
formed as vitamin E derivatives scavenge radicals, reforming
vitamin E that can scavenge more radicals. Preferred embodiments of
this invention harness this synergestic effect.
In addition, ascorbic acid can increase cyclo-oxygenase activity in
human cells. Cyclo-oxygenase is a key enzyme in the oxidation of
arachadonic acid, which leads the formation of prostaglandins which
in turn mediate inflammation.
The method of the present invention is particularly useful for the
prevention of skin damage which may result from exposure to
ultraviolet radiation, but, based upon the likely mechanism of
action, also is useful in general for treatment of any
radiation-induced skin damage, particularly that associated with
free radical related damage. As such, the topical application of
tocotrienol according to the invention can also be effective for
chronic administration to prevent the free radical damage seen in
the natural aging process of the skin and the free radical damage
caused by chronic exposure to sunlight. Tocotrienol or tocotrienol
and ascorbyl fatty acid esters can thus be added to dermatological
creams and emollients as well as to commercial suncreens to enhance
their anti-aging and anti-cancer activity. It can also be applied
as a treatment after burn.
Having described the invention with reference to particular
compositions, theories of effectiveness, and the like, it will be
apparent to those of skill in the art that it is not intended that
the invention be limited by such illustrative embodiments or
mechanisms, and that modifications can be made without departing
from the scope or spirit of the invention, as defined by the
appended claims.
* * * * *